The lab studies the quantitative operation of the systems that living cells use to sense, represent, transmit, and act upon information to make decisions that determine their future fates. One system under study is a prototypic cell signaling system in budding yeast, the pheromone response system. When appropriate (which is frequently) experimental work proceeds in concert with efforts to account for observed quantitative behaviors by simulation. Lab has extended similar work to systems operating in single cells of tissues in a metazoan, Caenorhabditis elegans. Because the lab studies system operation in single cells, we also study the causes and consequences of cell-to-cell variation in function of these systems, and the still-mysterious persistent cell physiological states that underlie much of this variation. Differences in these physiological states can have significant effects on the function of the organism that continue over the organism's life.
Work requires continual development and refinement of experimental and computational methods. One area of continual development is rapid means to generate new DNA constructions and make desired changes to the genomes of yeast and higher cells. Another is development of intracellular reporters that can quantify particular molecular events in living cells, together with microscopic, flow cytometric, and computational means to read the output of these reporters. Another is fluidic means to provide to the systems defined inputs. Much of this technology development finds application to other biological problems. Some of the current work is suggesting modalities for experimental manipulations and therapeutic interventions. Much of this technology development is in concert with closely collaborating labs in the US and abroad. The suggestions for possible therapeutic intervention may lead to collaborative applied work in 2015.
For the past three years, the lab has also included an experimental social science component. Some of this work continues under the aegis of the Center for Biological Futures, a two-year pilot project that brought together biologists with scholars in the social sciences and humanities, including anthropologists and philosophers, to better understand how biological knowledge and capability are shaping human affairs in the 21st century. This work included a significant collaboration with investigators at the University of Washington, in the project Biological Futures in a Globalized World. Brent and other lab members are frequently able to participate in government and other advisorial settings to help shape the overall course of future research, and all lab members are encouraged to identify and analyze how the outcomes of their research and the ongoing increases in biological knowledge and capability might shape human affairs.
1) 25 July 2014. Collaborating PI Jessica P. Houston receives a basic research award from The NCI’s Center to Reduce Cancer Health Disparities (CRCHD) at an investigators workshop for "Partnerships to Advance Cancer Health Equity" (PACHE) for collaborative work with Brent lab. See http://crchd.cancer.gov/news/spotlights/program-spotlights_PACHE_2014.html
2) 1 August 2014. Alexandra Ventura et al. " Utilization of extracellular information before equilibrium receptor binding expands and shifts the input dynamic range", accepted for PNAS. Work is in collaboration with the lab of Alejandro Colman-Lerner lab at the University of Buenos Aires. The mechanism, PRESS, is important for the operation of the large number of cell signaling systems that share certain dynamic properties.
3) 5 September 2014. Bryan Sands et al, "Measuring and sorting cell populations expressing isospectral fluorescent proteins with different fluorescence lifetimes" is accepted in PLOS ONE. Work is in collaboration with the lab of Jessica P. Houston at New Mexico State University. Going forward, we hope that altered-lifetime fluorescent proteins and appropriate equipment will enable us to quantify signaling events involving very small (<10) numbers of molecules.
4) 23 September 2014. Eddie Altszyler et al. "Impact of upstream and downstream constraints on a signaling module’s ultrasensitivity " is accepted in Physical Biology. Work is from collaborating Colman-Lerner lab. If certain "modules" in cell signaling systems generate steep (or "switchlike") response curves, and interface with certain kinds of upstream or downstream reactions, the "modules" can give response curves that are even steeper.